Preparation of targeted isoniazid microspheres.

Isoniazid (INH) albumin microspheres were prepared by two different stabilization processes: chemical denaturation using glutaraldehyde and heat denaturation. The extent of stabilization was characterized by the solubility of the microspheres. In vitro drug release rates were correlated to the stability of the microspheres and the results showed that the more denatured the albumin by heat stabilization, the slower the drug release rate. A factorial concept has been utilized to synthesize microspheres suitable for passive targeting to the lungs by varying protein concentration, stabilization temperature, time and aqueous volume. These factors significantly affected the sphere size, payload and a release profile of the drug. As the severity of the denaturation conditions increased, the payload decreased and the rate of drug release was slowed. The microspheres carrying isoniazid were followed in experimental animals to validate the targeting process.